When should iron supplementation in dialysis patients be avoided, minimized or withdrawn?

Parenteral iron is used to restore the body's iron pool before and during erythropoiesis-stimulating agent (ESA) therapy; together these agents form the backbone of anemia management in end-stage renal disease (ESRD) patients undergoing hemodialysis. ESRD patients receiving chronic intravenous iron products, which exceed their blood loss are exposed to an increased risk of positive iron balance. Measurement of the liver iron concentration (LIC) reflects total body iron stores in patients with secondary hemosiderosis and genetic hemochromatosis. Recent studies of LIC in hemodialysis patients, measured by quantitative MRI and magnetic susceptometry, have demonstrated a high risk of iron overload in dialysis patients treated with IV iron products at doses advocated by current anemia management guidelines for dialysis patients. Liver iron overload causes increased production of hepcidin and elevated plasma levels, which can activate macrophages of atherosclerotic plaques. This mechanism may explain the results of 3 long-term epidemiological studies which showed the association of excessive IV iron doses with increased risk of cardiovascular morbidity and mortality among hemodialysis patients. A more physiological approach of iron therapy in ESRD is needed. Peritoneal dialysis patients, hemodialysis patients infected with hepatitis C virus, and hemodialysis patients with ferritin above 1000 mu g/L without a concomitant inflammatory state, all require specific and cautious iron management. Two recent studies have shown that most hemodialysis patients will benefit from lower maintenance IV iron dosages; their results are applicable to American hemodialysis patients. Novel pharmacometric and economic approaches to iron therapy and anemia management are emerging which are designed to lessen the potential side effects of excessive IV iron while maintaining hemoglobin stability without an increase in ESA dosing.